Although there are a few medications designed to improvememory deficits in AD subjects, none of these treatments haltor slow down the progression, or delay onset of the disease ina significant manner. At best, the clinical benefits last 6 to 18months, and only in a modest subset of patients. Ourpioneering work on the role of genetic risk factors in diseaseetiology and therapy has allowed us to identify several geneticvariants that affect either, the age of onset, the rate ofprogression or the quality of the drug response to memoryenhancer medications. The most common genetic defectidentified so far involves a critical transporter of braincholesterol called apolipoprotein E (apoE), as well as many ofits accessory proteins called apoJ, ABCA1 and ABCA7,BuChE, FDPS, SREBF2, GGDPS and so the called HMGCR.Using this unique genetic information, we have characterizedthe biological functions of these key cholesterol transporter &modulators in the brain and screened a large number ofchemical entities capable of restoring apoE activity in the brainof affected AD subjects. This pioneering work led to thesuccessful identification of several potent apoE inducer agentswhich are now in pre-clinical development.